This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Phosphatidylinositol polyphosphates (PPIs) have recently emerged as key regulators of membrane trafficking pathways. We recently discovered that the PPI, phosphatidylinositol 3,5 bis phosphate (PI3,5)P2, is particularly critical for normal function of the nervous system. We found that very minor defects in the generation of (PI3,5)P2 are a significant risk factor in ALS. Moreover we recently found that the five proteins known to regulate PI3,5P2 are phosphorylated. The overall goal of this project is to determine the phosphorylation sites, and then to use a genetic approach to determine how phosphorylation regulates PI3,5P2 levels